Sensei Biotherapeutics Highlights PIKTOR Strategy Ahead of Endometrial Trial Readout

Key Points

• Faeth’s PIKTOR combines serabelisib and sapanisertib to inhibit the PI3K/AKT/mTOR pathway at multiple points, with the goal of improving pathway suppression across a broad range of alterations while using lower doses of each drug.
• The company expects top-line data later this year from the Phase II PIK-201 trial of PIKTOR plus paclitaxel in endometrial cancer. Earlier data showed improved progression-free survival with sapanisertib plus paclitaxel and promising responses from the three-drug combination, including three complete responses among five endometrial cancer patients.
• Reported Phase II safety findings included hyperglycemia in 14% of patients, with 5% Grade 3 events, and stomatitis in 14%, with no Grade 3 cases. Faeth is also studying PIKTOR in HR-positive, HER2-negative breast cancer, where it estimates a roughly $5 billion second-line market.

Faeth Therapeutics outlined its clinical strategy for PIKTOR, an oral combination designed to inhibit the PI3K/AKT/mTOR, or PAM, pathway at multiple points, during an analyst and investor event. The company is developing the regimen in endometrial cancer and hormone receptor-positive, HER2-negative breast cancer.

PIKTOR combines serabelisib, a PI3K-alpha inhibitor, with sapanisertib, an inhibitor of mTORC1 and mTORC2. Both drugs are taken orally with food Monday through Wednesday, followed by four days off treatment. Faeth Co-founder and CEO Anand Parikh said the multi-node approach is intended to more completely suppress the pathway while using lower doses of each drug than could be used individually.

“Single-node inhibitors, no matter the dose, cannot” completely disable the PAM pathway, Parikh said, citing feedback loops that can reactivate signaling when one node is blocked. He said Faeth aims to address patients with a broad range of PAM alterations, rather than only those with select PI3K mutations.

Endometrial Trial Readout Expected Later This Year

Faeth’s most advanced program is PIK-201, a Phase II trial of PIKTOR plus paclitaxel in endometrioid endometrial cancer. The company expects to report top-line data later this year.

Chief Medical Officer Debbie Chirnomas said endometrial cancer has the highest rate of PAM-pathway alterations among tumor types discussed by the company. She said the disease has approximately 68,000 new U.S. cases annually, while incidence has risen 26% and mortality has increased 36% over the past decade.

Faeth highlighted prior clinical findings involving the individual components and the combination. In a randomized Phase II trial involving advanced recurrent endometrial cancer, paclitaxel plus sapanisertib produced median progression-free survival of 5.6 months, compared with 3.7 months for paclitaxel alone, according to Chirnomas. In patients with endometrioid disease, median progression-free survival was 5.7 months with the combination and 3.3 months with paclitaxel alone.

In an earlier Phase Ib study of serabelisib, sapanisertib and weekly paclitaxel across advanced solid tumors, the company reported a 47% overall response rate and a 73% clinical benefit rate among response-evaluable patients. Among five endometrial cancer patients, Faeth reported four responses, including three complete responses, and median progression-free survival of 11 months. Chirnomas noted that these patients had received an average of four prior lines of therapy.

Parikh said the forthcoming PIK-201 update is expected to include approximately 40 response-evaluable patients, swimmer plots, landmark analyses, discontinuations and tolerability information. He said any decision to proceed to a registrational study would depend on the overall response rate, durability, safety profile and competitive environment.

Safety, Dose Selection and Pathway Inhibition

Faeth presented preclinical, pharmacokinetic and pharmacodynamic data supporting a regimen of 200 milligrams of serabelisib and 3 milligrams of sapanisertib. Chief Scientific Officer Oliver Maddocks said human skin-biopsy data from an earlier Takeda-led study indicated that the selected doses could achieve pathway inhibition without excessive drug exposure.

The company said the oral regimen remains above its IC90 exposure threshold for approximately three and a half days each week. Parikh contrasted that profile with intravenous gedatolisib, saying PIKTOR is intended to provide more time above IC90 while avoiding a high peak concentration that Faeth believes may contribute to stomatitis.

In a 22-patient data cut from the ongoing Phase II study, Chirnomas reported hyperglycemia in 14% of patients, including 5% Grade 3 events. Stomatitis occurred in 14% of patients, with no Grade 3 cases reported. She said the trial permitted patients with hemoglobin A1C levels of up to 8 and fasting glucose of up to 160, reflecting the high prevalence of obesity, prediabetes and diabetes among endometrial cancer patients.

Breast Cancer Program and Market Opportunity

Faeth is also enrolling PIK-101, a Phase Ib/II umbrella study in HR-positive, HER2-negative advanced breast cancer. The trial is evaluating PIKTOR with fulvestrant alone, fulvestrant plus palbociclib, and additional selective estrogen receptor degrader-based combinations. Initial data are expected at year-end 2027, Parikh said.

Chief Financial Officer Brian Stephenson said Faeth sees PIKTOR as potentially applicable regardless of PI3K or ESR1 mutation status. He estimated the second-line breast cancer market at approximately $5 billion and the second-line-plus endometrial cancer market at approximately $1.5 billion annually, based on available comparators.

Faeth said it is also evaluating potential expansion into additional tumor types and rare-disease opportunities.

About Sensei Biotherapeutics (NASDAQ:FTH)

Sensei Biotherapeutics, Inc is a clinical-stage biotechnology company focused on developing cancer immunotherapies designed to activate the immune system against tumors. The company's approach is intended to address immune suppression within the tumor microenvironment and potentially improve patients' responses to existing cancer treatments.

Sensei's pipeline has included antibody-based and vaccine-based immunotherapies. Its lead programs have included SNS-101, an antibody designed to target the VISTA immune checkpoint, and earlier ImmunoPhage-based programs intended to stimulate tumor-specific immune responses.

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